Study Shows Metabolic Strategy of Stressed Cell

Major St. Jude Study of Changes in Gene Activity and Metabolic
Enzymes Show How Cells Respond to a Sudden Decrease in the Levels
of Coenzyme A, a Key Player in the Daily Biochemical Routines that
Support Life

MEMPHIS, Tenn., March 23, 2007 /PRNewswire/ -- Investigators at
St. Jude Children's Research Hospital have mapped out many of the
dynamic genetic and biochemical changes that make up a cell's
response to a shortage of a molecule called Coenzyme A (CoA), a key
player in metabolism.

The results provide the most detailed look ever obtained of the
complex metabolic changes in a cell triggered by a potentially
fatal stress. CoA plays key roles in the cell's metabolism by
participating in biochemical reactions in specific areas throughout
the cell.

"The study provides the first detailed look at how the cell
shifts genetic gears to respond to a significant change in its
ability to carry on its daily metabolic chores," said Suzanne
Jackowski, Ph.D., a member of the St. Jude Infectious Diseases
department and the paper's senior author.

The St. Jude study is a significant contribution to the growing
field of metabolomics -- the study of the molecules involved in
metabolism, added Charles Rock, Ph.D., a member of the St. Jude
Infectious Diseases department and co-author of the paper. Coupled
with genetic studies of the cell, metabolomics is giving scientists
a more detailed picture of how the body maintains its health in
both normal environments and during times of stress, such as
starvation or disease.

A report on this work appears in the March issue of "Chemistry
and Biology."

The researchers studied the response to decreased CoA in a mouse
model by blocking CoA production. Following the shutdown of CoA
production, the cells quickly recycled CoA from other jobs so it
could concentrate all its efforts on a single task: extracting
life-supporting energy from nutrients in the mitochondria-the
powerhouses of the cell.

"We identified the metabolic rearrangements the cell undergoes
to ensure that the liver keeps CoA levels high enough to produce
glucose and the cells of the body maintain enough free CoA for the
mitochondria to keep producing ATP," said Yong-Mei Zhang, Ph.D., of
the St. Jude Infectious Diseases department and first author of the
report.

This work was supported in part by the National Institutes of
Health, a Cancer Center (CORE) Grant and ALSAC.

St. Jude Children's Research Hospital

St. Jude Children's Research Hospital is internationally
recognized for its pioneering work in finding cures and saving
children with cancer and other catastrophic diseases. Founded by
late entertainer Danny Thomas and based in Memphis, Tenn., St. Jude
freely shares its discoveries with scientific and medical
communities around the world. No family ever pays for treatments
not covered by insurance, and families without insurance are never
asked to pay. St. Jude is financially supported by ALSAC, its
fundraising organization. For more information, please visit
http://www.stjude.org.